Objective To search for and verify the genetic factors that lead to familial thoracic aortic aneurysm and dissection.Methods Patients with a family history were screened from clinical cases of thoracic aortic aneurysm and dissection,and their relevant clinical data were collected.After extracting the whole-genome DNA from the proband's blood samples,gene panel testing was carried out,and first-generation sequencing was used to verify the blood samples of the proband's immediate and collateral relatives.Meanwhile,relevant cell experiments were designed.First,the ACTA2-Leu195 * point mutation plasmid was constructed,and then the mutant plasmid and wild-type ACTA 2 were transfected into cells through expression plasmids respectively.After 48 hours,RNA and total protein were extracted,and the expression levels were detected by qPCR and Western blotting,respectively.Results Through high-throughput sequencing,the mutation site of c.583delC in the ACTA2 gene was found,and it was also confirmed that the heterozygous mutation at this site in the family was closely related to familial thoracic aortic aneurysm and dissection.The results of cell experiments showed that the mRNA and protein expression levels in the group transfected with the ACTA2-Leu195 * mutant plasmid were significantly decreased compared with those of the wild type,suggesting that the mutant could not express proteins normally.Conclusion Through clinical family studies and cell-level experiments,a new mutation site in ACTA2 leading to familial thoracic aortic aneurysm and dissection has been discovered,which provides a new approach for the screening,detection and clinical treatment of familial thoracic aortic aneurysm and dissection.

Objective To search for and verify the genetic factors that lead to familial thoracic aortic aneurysm and dissection.Methods Patients with a family history were screened from clinical cases of thoracic aortic aneurysm and dissection,and their relevant clinical data were collected.After extracting the whole-genome DNA from the proband's blood samples,gene panel testing was carried out,and first-generation sequencing was used to verify the blood samples of the proband's immediate and collateral relatives.Meanwhile,relevant cell experiments were designed.First,the ACTA2-Leu195 * point mutation plasmid was constructed,and then the mutant plasmid and wild-type ACTA 2 were transfected into cells through expression plasmids respectively.After 48 hours,RNA and total protein were extracted,and the expression levels were detected by qPCR and Western blotting,respectively.Results Through high-throughput sequencing,the mutation site of c.583delC in the ACTA2 gene was found,and it was also confirmed that the heterozygous mutation at this site in the family was closely related to familial thoracic aortic aneurysm and dissection.The results of cell experiments showed that the mRNA and protein expression levels in the group transfected with the ACTA2-Leu195 * mutant plasmid were significantly decreased compared with those of the wild type,suggesting that the mutant could not express proteins normally.Conclusion Through clinical family studies and cell-level experiments,a new mutation site in ACTA2 leading to familial thoracic aortic aneurysm and dissection has been discovered,which provides a new approach for the screening,detection and clinical treatment of familial thoracic aortic aneurysm and dissection.